Neonatal Malformations Research Articles

Research progress on risk factors of postoperative functional defecation disorder in anorectal malformation

AbstractAnorectal malformation (ARM) is a common congenital gastrointestinal malformation in neonates, which has complex pathological changes and unclear etiology. The only treatment modality currently available for ARMs is through surgical treatment to correct the deformity of the anal morphology and restore normal defecation function. In addition, the mortality rates of children with ARMs have significantly decreased as a result of recent advances in medical technology. It is important to note that despite the treatment of perianal anatomical deformities, approximately one‐third of ARM patients continue to experience functional defecation disorder (FDD), which includes fecal incontinence and constipation and negatively impacts the patient's quality of life. There are still numerous questions regarding the exact cause of FDD in ARM patients following surgery. It is generally accepted that the occurrence of FDD may be related to clinical staging, structural changes in the perianal rectal muscles, anomalies of the enteric nervous system, surgical injury, etc. However, some of these factors are still controversial and require additional study to be confirmed. In this paper, we review the risk factors for FDD following surgery in ARMs, which will help us to subsequently develop appropriate interventions to enhance the anal function and improve quality of life of children with ARMs.

The battle between the innate immune cGAS-STING signaling pathway and human herpesvirus infection.

The incidence of human herpesvirus (HHVs) is gradually increasing and has affected a wide range of population. HHVs can result in serious consequences such as tumors, neonatal malformations, sexually transmitted diseases, as well as pose an immense threat to the human health. The cGAS-STING pathway is one of the innate immune pattern-recognition receptors discovered recently. This article discusses the role of the cGAS-STING pathway in human diseases, especially in human herpesvirus infections, as well as highlights how these viruses act on this pathway to evade the host immunity. Moreover, the author provides a comprehensive overview of modulators of the cGAS-STING pathway. By focusing on the small molecule compounds based on the cGAS-STING pathway, novel targets and concepts have been proposed for the development of antiviral drugs and vaccines, while also providing a reference for the investigation of disease models related to the cGAS-STING pathway. HHV is a double-stranded DNA virus that can trigger the activation of intracellular DNA sensor cGAS, after which the host cells initiate a cascade of reactions that culminate in the secretion of type I interferon to restrict the viral replication. Meanwhile, the viral protein can interact with various molecules in the cGAS-STING pathway. Viruses can evade immune surveillance and maintain their replication by inhibiting the enzyme activity of cGAS and reducing the phosphorylation levels of STING, TBK1 and IRF3 and suppressing the interferon gene activation. Activators and inhibitors of the cGAS-STING pathway have yielded numerous promising research findings in vitro and in vivo pertaining to cGAS/STING-related disease models. However, there remains a dearth of small molecule modulators that have been successfully translated into clinical applications, which serves as a hurdle to be overcome in the future.

In the mind of the beholder: The effects of familiarisation on the perception of atypical infant facial configurations.

Infant facial attractiveness is an important facilitator for adult-infant caregiving behaviour. Disruption to typical infant facial configurations can, however, attenuate their perceived attractiveness, as rated by adult observers. Previous research has either focused on how ratings are affected by observer characteristics (e.g., male/female), or alterations to infant faces, either experimentally, or naturalistically induced, such as the presence of a cleft lip. Little research has however been conducted on the effects of observer experience on adult ratings of infant facial attractiveness. Such effects could inform clinical work and policies aimed at promoting positive perception of facial malformations. The present study thus explored the effects of familiarisation on how typical and atypical infant facial configurations are evaluated by adults. We recruited two groups of female participants and compared their subjective attractiveness ratings of infant faces (24 typical and 24 cleft-affected), at baseline, and at one-week post-test. Between the two assessments, one group (n = 41) underwent a week-long training phase, where they were familiarised with cleft lip/palate-related visual and informational stimuli, while the control group (n = 44) received no training. Significantly higher ratings were provided for faces of typically developing versus cleft-affected infants by both groups of participants at baseline. At post-test, this pattern of ratings was repeated in participants belonging to the control group, while familiarised participants showed an increase, compared to baseline, in their ratings of cleft-affected faces and no difference between their evaluation of the latter and that of typically developing faces. These findings extend our understanding of the observer's experience in the evaluation of infant faces, beyond the effects of the structural characteristics of the observed faces. Results also highlight familiarity as a potentially protective influence against the negative consequences of alterations to typical facial configurations, suggesting avenues for intervention in supporting adult caregivers in the context of neonatal facial malformations.

P-762 Exploring the Efficacy and Beneficial Population of Preimplantation Genetic Testing for Aneuploidy Start from Oocyte Retrieval Cycle: A Real-World Study

Abstract Study question Does preimplantation genetic testing for aneuploidy (PGT-A) increase chance of live birth among women undergoing IVF? What kind of women are most likely to benefit? Summary answer PGT-A is effective in people with specific indications, including maternal aged ≥38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions. What is known already As an embryo-selection technique, PGT-A is extensively used in in-vitro fertilization (IVF), but its efficacy and potential beneficial population is unclear. Study design, size, duration This was a retrospective cohort study. We analyzed data from women who underwent assisted reproduction treatment in the Reproductive and Genetic Hospital of CITIC-Xiangya. We included all first oocyte retrieval cycles from January 1, 2016, to November 31, 2019, and related fresh- and thawed-embryo transfer cycles up to November 31, 2020. Participants/materials, setting, methods The study cohort included 60,580 women. We used 1:3 propensity score matching to balance baseline data between women with PGT-A and without PGT-A. Stratified analyses according to age, body mass index, ovarian reserve/response, and potential indications were predesigned to explore benefits in sub-populations. The main outcome was cumulative live birth rate (CLBR) and the other observed outcomes including live birth rate (LBR), pregnancy loss, clinical pregnancy, pregnancy complications, newborn birth weight and neonatal malformation. Main results and the role of chance A total of 4,195 (95.1%) PGT-A users’ first oocyte retrieval cycles were matched to 10,140 non-users’ oocyte retrieval cycles. We found that women utilizing PGT-A had significantly lower CLBRs (27.5% vs. 31.1%; odds ratio (OR)=0.84, 95% confidence interval (CI), 0.78–0.91; P<.001) following the first oocyte retrieval cycle than did women not utilizing it. However, first transfers among women utilizing PGT-A had significantly higher pregnancy (63.9% vs. 46.9%; OR = 2.01, 95% CI, 1.81–2.23; P<.001) and live birth rates (LBR; 52.6% vs. 34.2%, OR = 2.13, 95% CI, 1.92–2.36; P<.001), as well as lower early miscarriage (12.8% vs. 20.2%; OR = 0.58, 95% CI, 0.48–0.70; P<.001), preterm birth (8.6% vs 17.3%; P<.001), and low birth weight rates (4.9% vs. 19.3%; P<.001). Moreover, subgroup analyses showed patients with maternal aged ≥38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions benefit from PGT-A, exhibiting significantly increasing LBRs following first transfer, without reducing CLBRs. Limitations, reasons for caution The retrospective design introduces inevitable bias. And the data originated from a single IVF center, thus, extrapolation of our findings may be limited, multi-center large data studies are needed to further confirm these findings. Wider implications of the findings Although PGT-A use does not increase and may decrease CLBR per oocyte retrieval cycle, it is effective in people with specific indications. Careful selection of suitable populations and proper clinical management for mosaic embryo transfer are important for effective PGT-A implementation. Trial registration number NA

Spectrum of Congenital Malformations in Neonates at a Rural Teaching Hospital — A Cross Sectional Observational Study

Introduction: The global estimates of congenital anomalies in neonates are 6% and few of them are severe enough to cause death. According to World Health Organization (WHO), congenital anomalies attribute to 17-42% of the infant mortality. Apart from causing death, they also contribute to preterm births, childhood and adult mortality, with significant repercussions in families. With the advancement of technology, there has been a decrease in the number of deaths due to other causes and there has been an increasing concern about congenital anomalies. This calls for an inquiry into the recent burden of congenital anomalies and their associated risk factors. Hence, the study was carried out. Objectives: 1. To assess the frequency and pattern of congenital anomalies. 2. To determine the factors associated with congenital anomalies. Materials & methods: This is an observational study which included all live born neonates with congenital anomaly/ies admitted to R L Jalappa Hospital (RLJH) and still born neonates or aborti with congenital anomaly/ies delivered in RLJH during the study period. A detailed history of the study participants was taken, and all the anomalies were coded as per the ICD coding system. For still born babies, aborti and neonatal deaths, infantogram, gross autopsy and histopathological examination findings were noted. Statistical analysis: Data was analysed using “Microsoft excel sheet” and the analysis was done using Statistical Package for Social Sciences (SPSS-16) software. Significance was defined as p<0.05. Results: Our hospital had 2,400 deliveries during the study period, out of which the frequency of congenital anomalies was 1.3%. As per the associated risk factors, 66.6% of the babies had no associated risk factors while the remaining 33.4% of the babies had an associated risk factor. Most commonly seen risk factor in the study was 3rd degree consanguinity (11.1%). As per the system involved, Musculoskeletal system involvement was seen in the majority (63.9%) of the neonates, followed by Cardiovascular system in 11.1%, Central Nervous System (CNS) in 8.3%, Genital system in 8.3%, Lymphatic system in 5.6%, Gastrointestinal system in 2.8%, Cutaneous in 2.8%, Oral cavity in 2.8% and syndromic anomaly in 2.8%. Conclusion: The prevalence of congenital anomalies is considerably high and increasing the awareness to prevent them is the need of the hour. Appropriate consideration should be given to reducing the risk factors and genetic counseling should be provided to parents with high risk. Keywords: Congenital malformations, Neonates, Congenital anomalies

11 Impact of a Cache Valley Fever Outbreak on Lambing Performance in a Landrace Hair Sheep Flock: A Case Study

Abstract Cache Valley Fever (CVF) is a mosquito-born, viral disease endemic to North America. While generally not associated with clinical symptoms in ewes, it affects fetal development during the first trimester of pregnancy resulting in malformations and pregnancy loss. A suspected outbreak of CVF was recorded in a flock of Barbados Blackbelly and St. Croix hair sheep managed under an 8-mo, accelerated mating system with ewes bred in March, July and November. The outbreak was associated with a July breeding, in a summer with unusually high rainfall and standing water in pastures. There had been no previous occurrence of CVF or other abortion storms in the flock (20+ years). Lambing outcome associated with the suspected outbreak of CVF was compared with that of the three prior July matings (CON). Ewes (n = 32-35) were managed in a pasture-based system under rotational grazing. Ewes were mated in two single sire groups of 16 to 18 ewes to like-breed sires each breeding season. Pregnancy was determined by transrectal ultrasound at end and 21 d after the 25-day breeding season. Ewes lambed on pasture, and lambs were tagged, and birth weights recorded within 24 hours. Blood samples were collected from all ewes following the CVF lambing and submitted for CVF antibody testing. All ewes showed CVF antibody titers. Pregnancy rate for the CVF lambing was not different from CON (85.7 vs. 89.8%; P = 0.512), whereas lambing rate was less in CVF for both ewes exposed (74.3 vs. 88.8%; P = 0.039) and ewes lambing (86.7 vs. 98.9%; P = 0.004). Incidence of stillborn and neonatal death of lambs was greater in CVF than CON (37.0 vs.5.6%; P = 0.002), as was the number of malformed lambs (13.0 vs. 0%; P < 0.001). Malformed lambs were associated with breech presentations. Litter size was not different in the CVF lambing (1.77 vs 1.86; P = 0.471), but lamb birth weight tended to be less (2.80 vs. 3.04 kg; P = 0.055) while ewe postpartum weight was not different (45.3 vs. 47.0 kg; P = 0.384). The outbreak of CVF reduced the lambing rate and increased the incidence of neonatal death and malformations. The outbreak occurred during a summer with unusually high rainfall and may be associated with changing weather patterns linked to climate change. Delaying summer breeding may be considered a mitigation strategy if feasible.

Early Cumulus Cell Removal Increases Cumulative Live Birth Rate while Having No Negative Effect on the Malformation Rate in In vitro Fertilization: A Propensity Score-Matched Cohort Study

Objective: The aim of this study was to investigate the efficacy and safety of early cumulus cell removal (ECCR) during human in vitro fertilization (IVF). Methods: A retrospective analysis was performed between January 2011 and December 2019. The study enrolled 1,131 couples who underwent IVF treatment with ECCR. After propensity score matching at a 1:1 ratio, 1,131 couples who underwent overnight coincubation of gametes were selected. The main outcome measure was the cumulative live birth rate. Secondary outcome measures included the cumulative pregnancy rate, polyspermy rate, available embryo rate, miscarriage rate, malformation rate, time to live birth, and oocyte-to-baby rate. Results: There were no significant differences found between the two groups in the polyspermy rate, available embryo rate, miscarriage rate, time to live birth, oocyte-to-baby rate, and neonatal congenital anomalies rate. The results of the study showed that ECCR was associated with a significantly higher cumulative live birth rate and cumulative pregnancy rate, along with a significantly lower fertilization rate. Conclusion: ECCR tended to confer increased cumulative live birth rate and had no negative effect on the neonatal malformation rate.

169 Exome Sequencing Implicates Endothelial Ras Signaling Network in Vein of Galen Aneurysmal Malformation

INTRODUCTION: Early neurovascular development is a complex and intricate process with devastating consequences when impaired. Vein of Galen Aneurysmal Malformations (VGAMs) are the most common and severe neonatal arteriovenous malformation and often present with high-output heart failure, hydrocephalus, neurodevelopmental delay, and brain hemorrhage. Despite their prevalence and severity, little is known regarding their genetic pathomechanism. METHODS: Genetic samples were collected from 114 VGAM probands, including 90 trios, from multiple sites. Collected specimens underwent whole exome sequencing, pathway analysis, and select ACVRL1 and EPHB4 mutations identified via sequencing were then studied in zebrafish models. RESULTS: Exome sequencing revealed a genome-wide significant burden of de novo mutations in Ras suppressor p120 Ras-GAP (RASA1) (enrichment = 324-fold; p = 4.8 x 10-7). Damaging transmitted variants were enriched in p120 Ras-GAP negative regulator Eph-B4 (EPHB4) (odds ratio = 27.4; p = 1.7 x 10-6). Eph-B4 missense variants caused loss of receptor tyrosine kinase activity constitutive Ras activation. Other probands had pathogenic variants in OMIM vascular disease genes PTNPN11, NOTCH1, and ACVRL1; the latter we found mutated in an ultra-rare multi-generational VGAM family. Pathway analysis identified enrichment of rare, damaging de novo and inherited variants in a network of interacting OMIM vascular disease genes involved in axon guidance (FDR = 2.3 x 10-5; enrichment = 3.65-fold). In zebrafish, the functional studies of ACVRL1 and EPHB4 confirmed severe vascular defects in mutant embryos. CONCLUSIONS: These results demonstrate that genetic regulation of a RASA1-centered Ras signaling hub is critical for cerebrovascular development and is impaired in VGAM pathogenesis. This finding has significant implications for the genetic counseling of patient families and the development of targeted therapeutics for VGAM neurovascular disorders.

Risk of obstetric and perinatal complications in women presenting with breast cancer during pregnancy and the first year postpartum in Sweden 1973-2017: A population-based matched study.

For women presenting with breast cancer during pregnancy, treatment guidelines were historically restricted to only surgical treatment. Over the past decades, chemotherapy administered during pregnancy has been gradually introduced. Although breast cancer treatments during ongoing pregnancy have been deemed safe, detailed information on potential obstetric risks is lacking. We aimed to assess the risk of adverse obstetric and perinatal outcomes of breast cancer in pregnancy and within 1 year postpartum and in relation to trimester at breast cancer diagnosis, tumor stage, and cancer treatment during pregnancy. Population-based matched study. Women diagnosed with breast cancer during pregnancy in 1973-2017 were identified in the Swedish Cancer Register and the Medical Birth Register, with additional information from the National Quality Register for Breast Cancer. Each birth with maternal breast cancer (n=208 pregnant, n=672 postpartum) was matched by age, calendar year, and birth order to 10 unexposed births from cancer-free women in the population (n=2080 and n=6720). Adjusted conditional logistic and multinomial regression models were used to estimate odds ratios and relative risk ratios, commonly denoted relative risks (RR) with 95% confidence intervals (CI), of adverse obstetric and perinatal outcomes. Breast cancer during pregnancy was associated with higher risks of preterm birth, both planned (RR 67.1, 95% CI 33.2-135.6) and spontaneous preterm birth (RR 3.8, 95% CI 2.0-7.5), and low birthweight (<2500 g: RR 7.5, 95% CI 4.9-11.3). The associated risks were higher if the breast cancer was diagnosed in the second trimester, and of similar magnitude irrespective of stage and treatment groups. There was a higher risk of low birthweight for gestational age (<25th centile) if breast cancer was diagnosed in the first trimester (RR 2.8, 95% CI 1.1-7.3). Risks of other pregnancy complications were similar to those of unexposed women, as were risks of neonatal mortality and malformations. Postpartum breast cancer was only associated with bleeding during pregnancy (RR 1.6, 95% CI 1.0-2.8). Preterm birth and related adverse outcomes were more common in women diagnosed with breast cancer during pregnancy. Reassuringly, breast cancer was not associated with other maternal pregnancy complications or adverse outcomes in children.

Single Stage Reconstructive Surgery to Treat Anorectal Malformations in Neonates; Ten Years Experience

Objective: To present single surgeon’s ten years’ experience of Single stage reconstructive surgery in 26 neonates born with anorectal malformations (ARMs) and review of literature. Methodology: This is a retrospective study of 26 neonates admitted in NICU with diagnosis of ARMs between period of June 2011 to Oct 2021 and managed by single stage reconstructive surgery with an average follow up of three years. All these patients were full term. The diagnosis was confirmed on clinical examination supported by cross table lateral film in prone position after 24 hours and ultrasound evaluation of level of rectal pouch. Single stage reconstructive surgery was done under general anesthesia within 24 to 48 hours after birth. The outcome of single stage reconstruction of neonates with anorectal malformations is evaluated post operatively during an average regular follow up of 3 years. Results: All the 26 neonates are treated by single stage reconstructive surgery between 24 to 48 hours after birth during the period from June 2011 to Oct 2021 who were admitted with anorectal malformations in NICU after excluding associated congenital anomalies.  All the patients had excellent cosmetic and functional outcome without significant problem of wound infection. Only 3 female patients with recto-vestibular fistula had mild superficial wound infection and were managed conservatively. Conclusion: Single stage reconstructive surgery to treat ARMs in neonates I effective, safe and feasible with good continence. It avoids morbidity and higher cost associated with three stage surgeries and colostomy. This fact may further be confirmed through multi-institutional experience in large number of patients.

Determining the incidence of heart malformations in neonates: A novel and clinically approved solution.

Screening for critical congenital heart defects should be performed as early as possible and is essential for saving the lives of children and reducing the incidence of undetected adult congenital heart diseases. Heart malformations remain unrecognized at birth in more than 50% of neonates at maternity hospitals. Accurate screening for congenital heart malformations is possible using a certified and internationally patented digital intelligent phonocardiography machine. This study aimed to assess the actual incidence of heart defects in neonates. A pre-evaluation of the incidence of unrecognized severe and critical congenital heart defects at birth in our well-baby nursery was also performed. We conducted the Neonates Cardiac Monitoring Research Project (ethics approval number: IR-IUMS-FMD. REC.1398.098) at the Shahid Akbarabadi Maternity Hospital. This study was a retrospective analysis of congenital heart malformations observed after screening 840 neonates. Using a double-blind format, 840 neonates from the well-baby nursery were randomly chosen to undergo routine clinical examinations at birth and digital intelligent phonocardiogram examinations. A pediatric cardiologist performed echocardiography for each neonate classified as having abnormal heart sounds using an intelligent machine or during routine medical examinations. If the pediatric cardiologist requested a follow-up examination, then the neonate was considered to have a congenital heart malformation, and the cumulative incidence was calculated accordingly. The incidence of heart malformations in our well-baby nursery was 5%. Furthermore, 45% of heart malformations were unrecognized in neonates at birth, including one critical congenital heart defect. The intelligent machine interpreted innocent murmurs as healthy heart sound. We accurately and cost-effectively screened for congenital heart malformations in all neonates in our hospital using a digital intelligent phonocardiogram. Using an intelligent machine, we successfully identified neonates with CCHD and congenital heart defects that could not be detected using standard medical examinations. The Pouya Heart machine can record and analyze sounds with a spectral power level lower than the minimum level of the human hearing threshold. Furthermore, by redesigning the study, the identification of previously unrecognized heart malformations could increase to 58%.

Fertility in Acromegaly: A Single-Center Experience of Female Patients During Active Disease and After Disease Remission.

Fertility represents a major concern in patients with acromegaly. The current retrospective study aimed to investigate gonadal function and fertility rates in acromegalic women. In this referral-center study, 50 acromegalic women with disease onset within reproductive age were evaluated for prevalence of gonadal dysfunction and infertility. Anthropometric, metabolic, hormonal parameters, and gynecological ultrasound were evaluated at diagnosis and after disease control. Data about menstrual disturbances, pregnancy, and polycystic ovarian morphology (PCOM) were investigated at disease onset, at diagnosis, and after disease control. At presumed disease onset, menstrual disturbances were reported in 32% of patients. Uterine leiomyoma, ovarian cysts, and PCOM were diagnosed in 18%, 12%, and 8%, respectively; 36.8% of patients were infertile. At diagnosis, menstrual disturbances were found in 58.1% (P = .02), being significantly more prevalent in patients with higher insulin-like growth factor-I quartiles (Q) (P = .03, Q1 vs Q4). Gynecological ultrasound revealed uterine leiomyoma, ovarian cysts, and PCOM in 39.1% (P = .04), 28.2% (P = .09), and 13% (P = .55), respectively. The infertility rate was 100% (P = .02). At disease control, menstrual disturbances were slightly decreased as compared to diagnosis (P = .09). Noteworthy, menstrual disturbances (P = .05) and particularly amenorrhea (P = .03) were significantly more frequent in patients with active disease duration greater than 5 years (median) as compared to those achieving disease control in less than 5 years. Among patients with pregnancy desire, 73.3% conceived at least once, with resulting infertility significantly decreased compared to diagnosis (26.7%; P = .01). At-term deliveries, preterm deliveries, and spontaneous abortions were recorded in 86.7%, 6.6%, and 6.6%, respectively, of the 15 pregnancies reported by the patients. No neonatal malformations and/or abnormalities were recorded. Gonadal dysfunction and infertility are common in acromegalic women within reproductive age, being directly influenced by disease status and/or duration.

Overcoming roadblocks in clinical innovation via high fidelity simulation: use of a phantom simulator to achieve FDA and IRB approval of a clinical trial of fetal embolization of vein of Galen malformations

BackgroundVein of Galen malformation (VOGM) is a rare, life-threatening vascular malformation in neonates and is treated with embolization. However, even at the most experienced centers, patients face high mortality and...

Identification of endocrine-disrupting chemicals targeting the genes and pathways of genital anomalies in males

Hypospadias and cryptorchidism are the most common congenital malformations in male neonates, both of which are also the important clinical manifestations of testicular dysgenesis syndrome and share a same origin. Many studies have suggested that prenatal exposure to endocrine-disrupting chemicals (EDCs) is associated with hypospadias and cryptorchidism development. However, the consistent mechanisms remain unclear. To identify the key EDCs, genes and biological networks related to the development of hypospadias and cryptorchidism respectively and commonly, we conduct the present study and found a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals. Transcriptome profiles were obtained from the Comparative Toxicogenomics Database (CTD). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses and protein-protein interaction (PPI) network were applied for integrative analyses. The rat model and molecular docking were applied to furtherly verifying the findings of the integrative analyses. Besides the highly related genes, most enriched pathways and chemicals for hypospadias and cryptorchidism respectively, we found hypospadias and cryptorchidism share many same highly associated EDCs (e.g., dibutyl phthalate) and genes (e.g., androgen receptor and estrogen receptor 1) through comparing highly related chemicals or genes of hypospadias and cryptorchidism respectively. GO and KEGG analysis showed that these same interactive genes were mainly enriched in steroidogenesis, response to steroid hormone and nuclear receptor activity. PPI network analysis identified 15 biological hub genes. Furtherly, hypospadias and cryptorchidism were induced by prenatal dibutyl phthalate exposure. Decreased serum testosterone level, downregulation of nuclear androgen-dependent and upregulation of cytoplasmic estrogen-dependent pathways may lead to hypospadias and cryptorchidism. This study proposed a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals and found that hypospadias and cryptorchidism share many same highly associated EDCs and genes.

Donated-embryo pregnancies are associated with increased risk of hypertensive disorders even for young recipients: a retrospective matched-cohort study

To determine whether pregnancies with donated embryos are at a higher risk of complications than the pregnancies from autologous frozen-thawed embryo transfer (FET). Anonymous, multicenter, comparative, observational, retrospective, matched-cohort study. Six French assisted reproductive technique centers from 2003 to2018. Seventy-three singleton pregnancies with donated embryos (exposed) and 136 singleton pregnancies after autologous FET (nonexposed) were matched at 7-8 weeks of gestation (pregnancy date, parity, and women's age) (2:1 ratio, respectively). In accordance with French practices, all women were <44 years old and donated embryos were discarded frozen embryos from other couples. Not applicable. Percentages of hypertensive disorders of pregnancy (HDPs) with donated embryos versus autologous FET. Groups were comparable (mean age: 34.5 years) and HDPs (24.6% vs. 11.9%) were significantly more frequent among the donated-embryo pregnancies, mostly in its severe forms (17.5% vs. 4.6%). In contrast, their respective isolated hypertension frequencies were comparable (7.0% vs. 7.3%). Multivariate analysis retained increased severe HDP risk with donated embryos (odds ratio 2.08 [95% confidence interval: 1.08-4.02]). No significant effect of endometrial preparation was observed. C-sections were more frequent for donated-embryo pregnancies (47.3% vs. 29.2%). Newborns from embryo donation or autologous FET were comparable for prematurity, birth weight and length, Apgar score, small for gestational age, large for gestational age, neonatal malformations, and sex ratio. Even for young women, the risk of severe HDP was 4 times higher for donated-embryo pregnancies than for autologous-FET pregnancies. The HDP risk must be acknowledged to inform donated-embryo recipients and provide careful pregnancy monitoring.

The epidemiology and disease burden of congenital TORCH infections among hospitalized children in China: A national cross-sectional study.

Congenital TORCH (Toxoplasma gondii (T. gondii), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV)) infections are associated with a variety of adverse prenatal and neonatal events, including miscarriage, malformations and developmental abnormalities, and they remain an issue that cannot be neglected in China. However, the current research focuses more on the general screening of TORCH in women of childbearing age, and the medical information of children hospitalized due to congenital and perinatal TORCH infections has not been described in detail. This study summarized and analyzed the epidemiological characteristics, clinical manifestations, length of stay (LOS), and the disease burden of hospitalized children diagnosed with congenital TORCH infections in 27 children's hospitals in China. Based on the face sheet of discharge medical records (FSMRs) of hospitalized children in 27 tertiary children's hospitals collected in the Futang Research Center of Pediatric Development and aggregated into FUTang Update medical REcords (FUTURE), we summarized and analyzed the epidemiological characteristics, clinical manifestations, LOS, the disease burden (in US dollars, USD) and potential risk factors for hospitalized children diagnosed with congenital toxoplasmosis, congenital rubella syndrome, congenital cytomegalovirus infection, and congenital HSV in 27 children's hospitals in China from 2015 to 2020. One hundred seventy-three patients aged 0-<1 year were hospitalized for congenital TORCH infections. Among infections with TORCH, hospitalization with congenital toxoplasmosis was the least common, with only five cases were reported (2.89%), while the LOS was the highest. The proportion of patients with congenital rubella syndrome (CRS) was 15.61%, and 86% of children hospitalized with CRS had cardiovascular malformations, and the economic burden was the highest. Congenital CMV infection cases accounted for the largest proportion (76.30%). Overall, 5.20% of patients were infected with HSV, and the expense of hospitalization for congenital HSV infection was relatively low. In the present study, the hospitalization proportion due to congenital TORCH infection was extremely low (17.56 per 100,000 neonates), indicating that China's congenital TORCH infection prevention and control policies remain effective. The lowest proportion of patients was hospitalized with congenital toxoplasmosis, while the LOS was the longest. The economic burden of CRS was heavy, and infants are recommended be vaccinated against RV in a timely manner. Congenital CMV infections accounted for the largest proportion of patients, suggesting that the disease burden of congenital CMV infection cannot be ignored, and the prevention of congenital CMV infection during pregnancy is still an important issue that needs to pay attention. The expense of hospitalization for congenital HSV infection was relatively low, while the disease burden increases significantly when patients develop complications. These data illustrate the importance of improving screening for congenital TORCH infections in the early diagnosis and treatment of neonatal patients.

The Prevalence of Chiari II Malformation in Neonates with Myelomeningocele at Ayub Teaching Hospital, KPK

Objective: Neural tube defects (NTDs) are common in northern areas of Khyber Pakhtunkhwa (KPK) and need a lot of community education for the parents regarding this disease, which impaired the patients for their whole life. The study aimed to assess the contribution of a family history of myelomeningocele and the resulting incidence of Chiari II malformation.&#x0D; Materials and Methods: A total of 131 patients were observed to determine the frequency of the Chiari II malformation in patients with myelomeningocele who presented in Ayub Teaching Hospital, Abbottabad. All neonates were sent to the radiology department for MRI. A repair procedure for meningomyelocele was done.&#x0D; Results: The mean age was 16.56 days. In 53.4% of neonates, there was a familial history of spinal dysraphism, while in 46.6% there was no familial history. Chiari II malformation was present in 23.7% of patients who presented with myelomeningocele. A significant difference (p-value &lt; 0.00001) existed between the presence/absence of a family history of myelomeningocele and Chiari II malformation out of the total.&#x0D; Conclusion: Early surgery, along with a multidisciplinary approach, provides the best opportunity for improved results and survival.&#x0D; Keywords: Meningomyelocele, Neural Tissue, Maternal Folate Intake, Meningomyelocele (MMC) Repair.

Патологія провізорних органів, ускладнення вагітності, пологів і стан малюків при вроджених вадах сечовидільної та нервової систем

Congenital malformations (CM) in fetuses and neonates belong to main causes of perinatal morbidity and mortality. Provision organs malformation and malfunction in such cohorts is less studied. The purpose - to analyze the course of pregnancy, the data of ultrasound imaging of provisional organs in the presence of CM of central nervous system (CNS) and/or of nephro-urinary system (NUS) in the fetus and newborn. Materials and methods. The results of prenatal and postnatal ultrasound, anamnestic and general clinical data of a sample of cases with prenatally diagnosed CM of CNS and/or NUS for the period 2017-2021 were analyzed. Results. There were 45 newborns with CNS malformations, and 54 newborns with CM of NUS. Malformations of NUS and/or CNS in the examined newborns were combined with anomalies of other systems in a third of cases - 29.6% and 31.1%, respectively. According to the results of prenatal ultrasound examinations, polyhydramnios (16.7%) was most often recorded in the pregnancies with fetal CM of NUS, and cases of fetal CM of CNS most commonly were registered placental hyperplasia (35.6%), fetal growth retardation (24.4%) and fetal distress (26.7%). Postnatally in both cohorts (with NUS malformations and with CNS malformations) a high rate of following complications were recorded: prematurity (16.7% and 15.6%, respectively), birth asphyxia (48% and 55.6%, respectively), and early neonatal death (11% and 6.6%). Сonclusions. Pregnant women with CM of CNS and/or NUS in the fetus belong to the group of high perinatal risk because of the high rate of perinatal complications. Information about the identified high perinatal risks in fetuses and newborns with CM of the CNS and/or NUS should be provided to parents and taken into account when planning management of pregnancy and labor.

Effects of inhaled nitric oxide (iNO) in pulmonary hypertension secondary to arteriovenous malformations: a retrospective cohort study from the European iNO registry

This study aims to assess the effects of inhaled nitric oxide (iNO) on oxygenation in the management of pulmonary hypertension (PH) secondary to arteriovenous malformations (AVMs) in neonates. This is a matched retrospective cohort study from January 1, 2013, to December 31, 2017. The European inhaled nitric oxide registry from 43 neonatal and pediatric ICUs in 13 countries across Europe was used to extract data. The target population was neonates treated with iNO for the management of PH. The cases (PH secondary to AVMs treated with iNO) were matched (1:4 ratio) to controls (PH without AVMs treated with iNO). The main outcome measure was the absolute change of oxygenation index (OI) from baseline to 60 min after starting iNO in cases and controls. The primary outcome of our study was that the mean absolute change in OI from baseline to after 60 min was higher among cases 10.7 (14), than in controls 6 (22.5), and was not statistically different between the groups. The secondary outcome variable — death before discharge — was found to be significantly higher in cases (55%) than in controls (8%). All the other variables for secondary outcome measures remained statistically insignificant. Conclusion: Infants with PH secondary to AVMs treated with iNO did not respond differently compared to those presented with PH without AVMs treated with iNO. Right ventricular dysfunction on echocardiography was higher in cases than controls (cases: 66.7% and controls: 28.6%) but was not statistically significant.What is Known:• Arterioenous malformation (AVM) is a well-known cause of persistent pulmonary hypertension in newborns. Inhaled nitric oxide (iNO) is most commonly used as first-line therapy for pulmonary hypertension in newborns.• Around 40–50% of vein of Galen malformations (VOGMs) are found to have congestive heart failure in the neonatal period.What is New:• Neonates may present with an isolated PH of the newborn as the main feature of the VOGMs. A large proportion of cases with AVMs have been associated with right ventricular cardiac dysfunction. • Results from one of the largest database registries in the world for iNO have been used to answer our research question.

Genetic Diagnostic Yield and Novel Causal Genes of Congenital Heart Disease.

Congenital heart disease (CHD) is the most common congenital malformation in fetuses and neonates, which also represents a leading cause of mortality. Although significant progress has been made by emerging advanced technologies in genetic etiology diagnosis, the causative genetic mechanisms behind CHD remain poorly understood and more than half of CHD patients lack a genetic diagnosis. Unlike carefully designed large case-control cohorts by multicenter trials, we designed a reliable strategy to analyze case-only cohorts to utilize clinical samples sufficiently. Combined low-coverage whole-genome sequencing (WGS) and whole-exome sequencing (WES) were simultaneously conducted in a patient-only cohort for identifying genetic etiologies and exploring candidate, or potential causative CHD-related genes. A total of 121 sporadic CHD patients were recruited and 34.71% (95% CI, 26.80 to 43.56) was diagnosed with genetic etiologies by low-coverage WGS and WES. Chromosomal abnormalities and damaging variants of CHD-related genes could explain 24.79% (95% CI, 17.92 to 33.22) and 18.18% (95% CI, 12.26 to 26.06) of CHD patients, separately, and 8.26% (95% CI, 4.39 to 14.70) of them have simultaneously detected two types of variants. Deletion of chromosome 22q11.2 and pathogenic variants of the COL3A1 gene were the most common recurrent variants of chromosomal abnormalities and gene variants, respectively. By in-depth manual interpretation, we identified eight candidate CHD-causing genes. Based on rare disease-causing variants prediction and interaction analysis with definitive CHD association genes, we proposed 86 genes as potential CHD-related genes. Gene Ontology (GO) enrichment analysis of the 86 genes revealed regulation-related processes were significantly enriched and processes response to regulation of muscle adaptation might be one of the underlying molecular mechanisms of CHD. Our findings and results provide new insights into research strategies and underlying mechanisms of CHD.